The overwhelming majority of such studies have used methods that directly or indirectly require the definition of a small set of collective variables (CVs).[1]}, [2]}, [3]}, [4]}, [5]}, [6]}, [7]}, [8]}, [9]}, [10]} The CVs are meant to encode the slow modes of the system such that, by applying a bias potential that is a function of the CVs, it is possible to remove the kinetic bottlenecks. Designing such CVs is often a non-trivial task and a successful choice of CVs demands physical intuition and an in-depth understanding of the system studied. Practical considerations suggest limiting the number of CVs used, and much ingenuity has been invested into condensing several physical parameters into a small number of CVs.[11]}, [2]}, [13]}
